More deaths raise further questions about Adaptimmune

Adaptimmune yesterday played down another three deaths with its T-cell receptor therapies, but its projects have now been linked with five treatment-related fatalities, raising more questions about its technology. And recent staff departures will have done nothing to boost investor confidence. The latest deaths came in trials of ADP-A2M4 and ADP-A2M10; the latter was also linked to a fatality in 2017, but this was deemed not treatment related. The company blamed two of the new deaths on a high dose of cyclophosphamide used in the preconditioning regimen, but admitted that it was difficult to rule out an effect of the T-cells completely. And executives insisted that the other death, due to a stroke, was not treatment related, but conceded that ADP-A2M4 probably caused prior neurotoxicity. Adaptimmune has deprioritised ADP-A2M10, but put this down to efficacy rather than safety reasons. The group’s president of R&D, Rafael Amado, announced his departure yesterday, joining James Noble, who said he was stepping down as chief executive in June. Issues with the TCR technology could also be bad news for Glaxosmithkline, which licensed Adaptimmune's NY-ESO-targeting project; a patient death in 2015 led to a clinical hold, but this was later lifted.

Taking a toll? Fatalities with Adaptimmune-originated projects
Project Target Issue Note
ADP-A2M4 Mage-A4 Aug 2019: one death due to pancytopenia (treatment related), one due to stroke (not treatment related)  
ADP-A2M10 Mage-A10 Aug 2019: one death due to pancytopenia (treatment related);
Nov 2017: one death due to pulmonary failure (not treatment related)
Deprioritised Aug 2019
GSK3377794* NY-ESO Aug 2015: one death leading to clinical hold (treatment related) Second (non safety-related) clinical hold in 2016, later lifted
Mage-A3 TCR   Mage-A3 2011/12: two patient deaths due to heart failure (treatment related) Programme terminated
*Licensed to Glaxosmithkline; Source: company releases, SEC filings.

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